This work is directed toward elucidation of the molecular bases and thermodynamic properties of the gelatin of sickle cell hemoglobin, and also toward aspects of the relations between the molecular structure of hemoglobins in general and their allosteric function. In respect to hemoglobin S, studies of polymerization and phase changes in hemoglobin S gels will be carried out in order to ascertain the microscopic and macroscopic phases which exist under a variety of conditions and, with this information, in order to attempt delineation of the particular phases which are most pathogenic within the red cell. While sickled red cells are considered to consist of tactoidal arrays of hemoblobin S fibers, this work will consider the possible roles of isotropically oriented fibers and of a possible dense fibrous or quasi-crystalline phase in inducing sickling and in limiting the deformability of erythrocytes, thus impeding their passage through capillaries. A variety of physical methods, including particularly ultracentrifugation, light scattering and viscosity will be used. Other aspects of this work are directed to ascertaining the effects of various small molecules which bind non-covalently to hemoglobin on gelation. Through these approaches it is hoped (a) to gain understanding of basic mechanisms of gelation, (b) to find means of inhibiting gelation and (c) to determine factors which alter the natural history of sickle cell disease by inducing or preventing sickle crises. BIBLIOGRAPHIC REFERENCES: Herzfeld, J. and Briehl, R.W. Interrelations Between Tactoid Formation and Rod Length in Linear Polymers. Fed. Proc. 36:758, 1977. Herzfeld, J. and Briehl, R.W. Phase Transitions in Reversibly Polymerizing Systems. Federation European Biochemical Societies, Copenhagen, 1977, in press.